NCT04320797

Brief Summary

Urinary T-lymphocytes may be predictive for clinical outcome in patients with lupus nephritis. The investigators hypothesize that the amount of CD4+ effector/memory T-cells in urine at time of diagnosis predicts the outcome of patients with active lupus nephritis (LN) after 6 months of therapy. In a prospective, six-months follow-up study patients' urine will be analysed by flow cytometry every 60 days (+/- 10d). Treatment will be performed to the discretion of the treating clinician. After 6 months of treatment response will be determined as either complete response or partial response.

Trial Health

47
At Risk

Trial Health Score

Automated assessment based on enrollment pace, timeline, and geographic reach

Trial has exceeded expected completion date
Enrollment
79

participants targeted

Target at P50-P75 for all trials

Timeline
Completed

Started Jul 2019

Typical duration for all trials

Geographic Reach
2 countries

2 active sites

Status
unknown

Health score is calculated from publicly available data and should be used for screening purposes only.

Trial Relationships

Click on a node to explore related trials.

Study Timeline

Key milestones and dates

Study Start

First participant enrolled

July 30, 2019

Completed
8 months until next milestone

First Submitted

Initial submission to the registry

March 23, 2020

Completed
2 days until next milestone

First Posted

Study publicly available on registry

March 25, 2020

Completed
2.4 years until next milestone

Primary Completion

Last participant's last visit for primary outcome

September 1, 2022

Completed
Same day until next milestone

Study Completion

Last participant's last visit for all outcomes

September 1, 2022

Completed
Last Updated

March 9, 2022

Status Verified

March 1, 2022

Enrollment Period

3.1 years

First QC Date

March 23, 2020

Last Update Submit

March 8, 2022

Conditions

Lupus Nephritis

Keywords

lupus nephritissystemic lupus erythematodesurinary biomarkeroutcomepredictionurinary effector memory T lymphocytesglomerulonephritisnon-invasive biomarkerflow cytometrytreatment outcomeCD4-positive T-lymphocytes/immunology

Outcome Measures

Primary Outcomes (1)

  • Phenotype of CD4+ T cells at time point 0 predictive of clinical outcome in patients with lupus nephritis

    Urinary CD4+ effector/memory T cell counts at time point 0 (time of diagnosis) predict clinical outcome (complete or partial response) after 6 months of treatment in patients with lupus nephritis. The frequency of effector/memory CD4+ T lymphocytes is higher in patients with non- or partial response. * Complete response at 24 weeks: the return to within 10 percent of normal values of serum creatinine levels, proteinuria, and urine sediment. * Partial response at 24 weeks: improvement of 50 percent in all abnormal renal measurements, without worsening - within 10 percent - of any measurement

    6 months

Secondary Outcomes (5)

  • Distinction between proliferative LN (class III and class IV) and non-proliferative LN (classes I, II and VI)

    6 months

  • Analysis of patient with persistent renal abnormalities as partial response

    6 months

  • Prediction of complete or partial response according to normalization of the amount of urinary T cells at time point 2 and 4

    6 months

  • Phenotype of CD8+ T cells at time point 0 predictive of clinical outcome in patients with lupus nephritis

    6 months

  • Diagnosis of proliferative lupus nephritis in patients with systemic lupus erythematodes (SLE)

    6 months

Study Arms (2)

Active lupus nephritis

Patients with proliferative lupus nephritis (Class III and IV)

Diagnostic Test: Flow cytometry analysis of urine samples

Control

Patients with systemic lupus erythematodes without lupus nephritis or lupus nephritis I, II or VI

Diagnostic Test: Flow cytometry analysis of urine samples

Interventions

Flow cytometry analysis of urine samplesDIAGNOSTIC_TEST

Urine samples will be conserved and frozen upon arrival. All samples will be stained according to T cell and TEC (tubular epithelial cells) panel with fluorochromes. T cell panel: CD3, CD4, CD8, CCR7, CD45RO, CD28, CD279; TEC panel: vimentin, cytokeratine, CD10, CD13, CD227, CD326

Active lupus nephritisControl

Eligibility Criteria

Age18 Years+
Sexall
Healthy VolunteersNo
Age GroupsAdult (18-64), Older Adult (65+)
Sampling MethodProbability Sample
Study Population

Patients at medical wards of Charité Universitätsmedizin Berlin and University College London

You may qualify if:

  • Biopsy proven lupus nephritis
  • In absence of a biopsy a SLEDAI of at least 10 \& at least two renal elements of the renal SLEDAI (rSLEDAI)
  • Informed consent
  • Diagnosis of SLE according to the American College of Rheumatology (ACR) criteria

You may not qualify if:

  • Biopsy-proven non-SLE related disease
  • Urinary tract infection
  • Active menstrual bleeding
  • Kidney transplantation during observation time

Contact the study team to confirm eligibility.

Sponsors & Collaborators

Study Sites (2)

Charité - Universitätsmedizin Berlin

Berlin, 10117, Germany

Location

The Royal Free London

London, NW3 2QG, United Kingdom

Location

Related Publications (4)

  • Enghard P, Rieder C, Kopetschke K, Klocke JR, Undeutsch R, Biesen R, Dragun D, Gollasch M, Schneider U, Aupperle K, Humrich JY, Hiepe F, Backhaus M, Radbruch AH, Burmester GR, Riemekasten G. Urinary CD4 T cells identify SLE patients with proliferative lupus nephritis and can be used to monitor treatment response. Ann Rheum Dis. 2014 Jan;73(1):277-83. doi: 10.1136/annrheumdis-2012-202784. Epub 2013 Mar 8.

    PMID: 23475982BACKGROUND

  • Arazi A, Rao DA, Berthier CC, Davidson A, Liu Y, Hoover PJ, Chicoine A, Eisenhaure TM, Jonsson AH, Li S, Lieb DJ, Zhang F, Slowikowski K, Browne EP, Noma A, Sutherby D, Steelman S, Smilek DE, Tosta P, Apruzzese W, Massarotti E, Dall'Era M, Park M, Kamen DL, Furie RA, Payan-Schober F, Pendergraft WF 3rd, McInnis EA, Buyon JP, Petri MA, Putterman C, Kalunian KC, Woodle ES, Lederer JA, Hildeman DA, Nusbaum C, Raychaudhuri S, Kretzler M, Anolik JH, Brenner MB, Wofsy D, Hacohen N, Diamond B; Accelerating Medicines Partnership in SLE network. The immune cell landscape in kidneys of patients with lupus nephritis. Nat Immunol. 2019 Jul;20(7):902-914. doi: 10.1038/s41590-019-0398-x. Epub 2019 Jun 17.

    PMID: 31209404BACKGROUND

  • Dolff S, Abdulahad WH, Arends S, van Dijk MC, Limburg PC, Kallenberg CG, Bijl M. Urinary CD8+ T-cell counts discriminate between active and inactive lupus nephritis. Arthritis Res Ther. 2013 Feb 27;15(1):R36. doi: 10.1186/ar4189.

    PMID: 23445537BACKGROUND

  • Kopetschke K, Klocke J, Griessbach AS, Humrich JY, Biesen R, Dragun D, Burmester GR, Enghard P, Riemekasten G. The cellular signature of urinary immune cells in Lupus nephritis: new insights into potential biomarkers. Arthritis Res Ther. 2015 Apr 3;17(1):94. doi: 10.1186/s13075-015-0600-y.

    PMID: 25890061BACKGROUND

Biospecimen

Retention: SAMPLES WITH DNA

urine, lymphocytes

MeSH Terms

Conditions

Lupus NephritisGlomerulonephritis

Condition Hierarchy (Ancestors)

NephritisKidney DiseasesUrologic DiseasesFemale Urogenital DiseasesFemale Urogenital Diseases and Pregnancy ComplicationsUrogenital DiseasesMale Urogenital DiseasesLupus Erythematosus, SystemicConnective Tissue DiseasesSkin and Connective Tissue DiseasesAutoimmune DiseasesImmune System Diseases

Study Officials

  • Philipp Enghard, PD Dr. med.

    Charite University, Berlin, Germany

    PRINCIPAL INVESTIGATOR

Study Design

Study Type
observational
Observational Model
CASE CONTROL
Time Perspective
PROSPECTIVE
Sponsor Type
OTHER
Responsible Party
PRINCIPAL INVESTIGATOR
PI Title
PD Dr. med.

Study Record Dates

First Submitted

March 23, 2020

First Posted

March 25, 2020

Study Start

July 30, 2019

Primary Completion

September 1, 2022

Study Completion

September 1, 2022

Last Updated

March 9, 2022

Record last verified: 2022-03

Locations

DE(1)GB(1)